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. 2022 Oct 17;5(6):e892.
doi: 10.1002/hsr2.892. eCollection 2022 Nov.

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID-19 patients: A systematic review and meta-analysis

Dena Firouzabadi  1   2 , Fatemeh Kheshti  3 , Saeed Abdollahifard  3   4 , Erfan Taherifard  5 , Mohammad Reza Kheshti  3
Affiliations

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID-19 patients: A systematic review and meta-analysis

Dena Firouzabadi et al. Health Sci Rep. .

Abstract

Background and aim: Due to the high social and economic burden and also mortality and morbidity caused by coronavirus disease 2019 (COVID-19) in the past few years, researchers have aimed at finding solutions to suppressing the severity of infection. Recently, selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) have been investigated as an adjuvant treatment for COVID-19. The aim of the current study was to investigate the impact of SSRI/SNRIs on outcomes of COVID-19 patients.

Methods: In this systematic review and meta-analysis, a comprehensive search strategy consisting of relevant words was performed by two researchers in PubMed, Scopus and EMBASE libraries. Studies reporting the effect of SSRI and/or SNRI use in COVID-19 patients' outcome were included. Hospitalization, mortality, hospitalization event, and length of hospital stay were considered as main outcomes of this study. Analysis was carried out using Comprehensive Meta-Analysis (CMA-version 2) and final data were reported as odds ratio (OR) and 95% confidence interval (CI).

Results: Our search led to the final selection of 9 articles including 15,287 patients. The effect of fluvoxamine, fluoxetine, and the overall effect of SSRI/SNRI use on mortality of COVID-19 patients were investigated in 3, 2, and 7 articles, respectively. The results of our analyses showed that these medications could significantly decrease mortality of COVID-19 patients (OR and 95% [CI]: 0.595 [0.467-0.758], 0.620 [0.469-0.821], and 0.596 [0.437-0.813]). The effect of SSRI/SNRIs on hospitalization events of COVID-19 patients was not significant (OR: 0.240% and 95% CI: 0.041-1.4). Also, length of hospital stay was longer in patients who administrated SSRIs.

Conclusion: According to this study's results, SSRI/SNRIs may be effective in reducing mortality of COVID-19 patients, suggesting the superiority of fluvoxamine to fluoxetine. The safety profile and affordable cost of SSRI/SNRIs for a short-term use may be other reasons to propose them as beneficial medications in preventing mortality in COVID-19.

Keywords: COVID‐19; SNRI; SSRI; selective serotonin reuptake inhibitors; serotonin‐norepinephrine reuptake Inhibitor.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of included studies for determining the effect of SSRI/SNRI on clinical outcomes of COVID‐19 patients. COVID‐19, coronavirus disease 2019; PRISMA, Preferred Reporting Items for Systematic reviews and Meta‐Analyses; SNRI, serotonin‐norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor
Figure 2
Figure 2
Forest plot of included studies investigating the effect of SSRI/SNRI on mortality of COVID‐19 patients. I 2 = 70.99, Eager's test (p value) = 0.052, sensitivity analysis = not significant. COVID‐19, coronavirus disease 2019; SNRI, serotonin‐norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor
Figure 3
Figure 3
Forest plot of included studies investigating the effect of SSRI on hospitalization events of COVID‐19 patients. I 2 = 55.92, Eager's test (p value) = 0.096, Sensitivity analysis = not significant. COVID‐19, coronavirus disease 2019; SNRI, serotonin‐norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor
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